N-methyl-N-nitrosourea-induced apoptosis of photoreceptor cells in Sprague-Dawley rats via nuclear factor-κB  

作　　者：YANGJin-nan LUOLin LINShao-chun CHENJin-mao LIDai HUShi-xing 

机构地区：[1]ZhongshanOphthalmicCentre,SunYat-senUniversity,Guangzhou510060,China [2]DepartmentofPharmacy,XinxiangMedicalCollegeofHenanProvince,Xinxiang453003,China

出　　处：《Chinese Medical Journal》2005年第13期1081-1086,共6页中华医学杂志（英文版）

基　　金：ThisstudywassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina(No 30300467)

摘　　要：Background Previous studies have showed that photooxidative stress can leadto down-modulation of nuclear factor-κappa B ( NF-κB ) activity causing apoptosis of culturedphotoreceptor cells. This study aimed at investigating whether NF-κB was involved in photoreceptorcells apoptosis induced by N-methyl-N-nitrosourea (MNU) in rats. Methods A single intraperitonealinjection of 60 mg/kg MNU was given to 50-day-old female rats. At different intervals after MNUtreatment, the animals were sacrificed. Retinal damage was examined by a light microscope. Theapoptotic index of the photoreceptor cells was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL). NF-κB was analysed by Western blotand Transcriptin Factor Assay Kits. Results The pyknosis of the photoreceptor nuclei and thedisorientation of the outer segment of the photoreceptor layer was seen after MNU treatment for 24hours. The outer nuclear layer and photoreceptor layer were almost completely lost at 7 days.Photoreceptor cells apoptosis reached the peaked value at 24 hours. In apoptotic cascade, theprotein levels of NF-κB p65 were only detected after MNU treatment for 12 and 24 hours in thenucleus. Conversely, the amounts of IκBα were markedly increased in the cytoplasm as well as inthe nucleus. The activity of NF-κB p65 in the nucleus was down-modulated in the end. ConclusionsMNU-induced photoreceptor cell destruction was attributed to the apoptotic process bydown-regulating the activation of NF-κB p65.Background Previous studies have showed that photooxidative stress can leadto down-modulation of nuclear factor-κappa B ( NF-κB ) activity causing apoptosis of culturedphotoreceptor cells. This study aimed at investigating whether NF-κB was involved in photoreceptorcells apoptosis induced by N-methyl-N-nitrosourea (MNU) in rats. Methods A single intraperitonealinjection of 60 mg/kg MNU was given to 50-day-old female rats. At different intervals after MNUtreatment, the animals were sacrificed. Retinal damage was examined by a light microscope. Theapoptotic index of the photoreceptor cells was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL). NF-κB was analysed by Western blotand Transcriptin Factor Assay Kits. Results The pyknosis of the photoreceptor nuclei and thedisorientation of the outer segment of the photoreceptor layer was seen after MNU treatment for 24hours. The outer nuclear layer and photoreceptor layer were almost completely lost at 7 days.Photoreceptor cells apoptosis reached the peaked value at 24 hours. In apoptotic cascade, theprotein levels of NF-κB p65 were only detected after MNU treatment for 12 and 24 hours in thenucleus. Conversely, the amounts of IκBα were markedly increased in the cytoplasm as well as inthe nucleus. The activity of NF-κB p65 in the nucleus was down-modulated in the end. ConclusionsMNU-induced photoreceptor cell destruction was attributed to the apoptotic process bydown-regulating the activation of NF-κB p65.

关 键 词：METHYLNITROSOUREA PHOTORECEPTORS APOPTOSIS nuclear factor-kappa B 

分 类 号：R77[医药卫生—眼科]